Second case report of del(4) (q25q27) and review of the literature

We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion.     

Interstitial deletion of 10q: Clinical features and literature review

We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley-Liss, Inc.     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Isochromosome 18q in a girl with holoprosencephaly,DiGeorge anomaly,and streak ovaries

We report on the clinical and pathologic findings in a girl with isochromosome 18q (46, XX,i(18q)) who had combined manifestations of monosomy 18p and trisomy 18q. Major congenital anomalies included premaxillary agenesis, alobar holoprosenphaly, double Outlet right ventricle, DiGeorge anomaly and streak ovaries. The clinical spectrum in i(18q) is very broad. © 1993 Wiley-Liss, Inc.     

Decreased antibody-dependent cellular cytotoxicity in minimal change nephrotic syndrome

Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and -interferon (IFN-) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN- production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS.     

急性脑梗死患者血清CTRP-3、D-二聚体、sTREM2水平及相关临床特征与溶栓后出血性转化的关系

目的 探讨急性脑梗死患者血清补体C1q/肿瘤坏死因子相关蛋白3（CTRP-3）、D-二聚体、可溶性髓样细胞触发受体2（sTREM2）水平及相关临床特征与溶栓后出血性转化（HT）的关系。方法 回顾性分析2018年9月—2022年9月在青海省人民医院接受溶栓治疗的120例急性脑梗死患者的临床资料,根据患者溶栓后是否发生HT分为HT组（30例）、非HT组（90例）。比较两组患者的临床资料及血清CTRP-3、D-二聚体、sTREM2水平。采用多因素逐步Logistic回归分析急性脑梗死患者溶栓后发生HT的危险因素;绘制受试者工作特征（ROC）曲线,分析急性脑梗死患者溶栓后HT预测模型预测HT发生的价值。结果 HT组心房颤动（以下简称房颤）、大面积脑梗死、入院NIHSS评分≥ 15分占比高于非HT组（P <0.05）,血清CTRP-3水平低于非HT组（P <0.05）,D-二聚体、sTREM2水平高于非HT组（P <0.05）。血清CTRP-3、D-二聚体、sTREM2水平预测急性脑梗死患者溶栓后发生HT的敏感性分别为66.7%（95% CI：0.598,0.756）、70.0%（95% CI：0.607,0.812）、80.0%（95% CI：0.714,0.889）,特异性分别为73.3%（95% CI：0.636,0.821）、86.7%（95% CI：0.778,0.923）、86.7%（95% CI：0.747,0.942）。多因素Logistic逐步回归分析结果显示,房颤［O^R=1.237（95% CI：1.103,1.387）］、大面积脑梗死［O^R=2.338（95% CI：1.292,4.231）］、入院NIHSS评分≥ 15分［O^R=2.087（95% CI：1.231,3.538）］、CTRP-3 ≤ 269.265 μg/L ［O^R=3.006（95% CI：1.508,5.992）］、D-二聚体≥ 2.625 mg/L ［O^R=2.649（95% CI：1.374,5.107）］、sTREM2 ≥ 314.675 ng/L ［O^R=2.328（95% CI：1.411,3.841）］是急性脑梗死患者溶栓后发生HT的危险因素（P <0.05）。根据多因素Logistic逐步回归分析结果建立急性脑梗死患者溶栓后HT预测模型,Logit（P） = -33.887 + 0.213×房颤+ 0.849×大面积脑梗死+0.736×入院NIHSS评分+ 1.101×CTRP-3 + 0.974×D-二聚体+ 0.845×sTREM2;ROC曲线分析结果表明,预测模型预测HT发生的敏感性为93.3%（95% CI：0.841,0.991）,特异性为87.8%（95% CI：0.808,0.976）。结论 血清CTRP-3、D-二聚体、sTREM2水平与急性脑梗死患者溶栓后HT有关,预测价值较高,且急性脑梗死患者溶栓后HT预测模型预测HT优于各项指标单独预测。     

Preponderance of β- over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium

Summary [³H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K _d = 0.25 nmol/l and B _max = 27 fmol/mg protein in the right ventricle). [³H]CGP-12177, a -adrenoceptor ligand, bound to the membrane fraction with a _{K d} value of 0.29 nmol/l and a B _max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 ol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both - and -adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, -adrenoceptors predominate over -adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of -adrenoceptors is not especially high when compared with other species. Send offprint requests to M. Endoh at the above address     

Testosterone in a Cyclodextrin-Containing Formulation: Behavioral and Physiological Effects of Episode-like Pulses in Rats

Testosterone, administered in the form of an inclusion complex with 2-hydroxypropyl--cyclodextrin by subcutaneous injection, enters the circulation in a manner markedly similar to the natural episodic release by the testes. The effects of a regimen of once-a-day administration of complexed testosterone to adult (castrated or intact) rats and to senescent (intact) rats were investigated. Although this procedure left the castrated animals with concentrations of circulatory hormone far below physiological levels for much of the day, a significant improvement in androgen-sensitive behavior and physiology was obtained. Furthermore, the testosterone effects were more pronounced when high doses were used periodically rather than when the same total amount of testosterone was equally divided among doses. The same supplementation to intact rats intensified androgen-sensitive behavior and physiology over normal levels. In senescent rats uniform pulses of the testosterone complex also improved behavior and physiology. Specifically, spermatogenesis was stimulated and, notably, the treatment increased muscle weight without substantial enlargement of the prostate. Since the testosterone–cyclodextrin complex also can be effectively administered as a sublingual tablet, the data suggest that similar regimens may be recommended for elderly men suffering from decreases in muscle mass.     

Compartmentation of cardiac adenine nucleotides and formation of adenosine

Summary After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either¹⁴C-adenine or¹⁴C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 35-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substance. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart.Our findings provide evidence that at least two different adenine nucleotide compartments of the heart serve as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.A preliminary report of part of this work appeared in Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction Vol. 7 of Recent advances in studies on cardiac structure and metabolism. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976A preliminary report of part of this work appeared in Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarction Vol. 7 of Recent advances in studies on cardiac structure and metabolism. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976     

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.